The uptake of active glycoprotein lysosomal enzymes occurs, in part, through the mechanism of adsorptive pinocytosis. Receptors for various parts of the enzyme molecule as ligands are present on the plasma and organelle membranes. It is the purpose of this project to study these receptors and utilize them for targeting enzymes to cells. These binding capacities may also play a role in localizing glycoproteins within the cell and thus may have a bearing on the survival of enzymes that have been incorporated into the cell. Studies are directed toward increasing the survival of exogenous enzymes within certain subcellular organelles. The goal is to increase the interaction of exogenous enzyme with stored material in the cell and increase the efficiency of enzyme replacement. Studies will be carried out in rats and later in human macrophages. Studies of the distribution of glucocerebrosidase confirm that infused enzyme can reach the lysosome and does not require the ligand mannose-6-phosphate (M-6-P). Moreover, hepatocytes lack an endocytic lectin with M-6-P specificity.